Abstract
Objectives
Blood biomarkers have the potential to transform diagnosis and prognosis for multiple neurological indications. Establishing normative data is a critical benchmark in the analytical validation process. Normative data are important in children as little is known about how brain development may impact potential biomarkers. The objective of this study is to generate pediatric reference intervals (RIs) for serum neurofilament light (NfL), an axonal marker, and glial fibrillary acidic protein (GFAP), an astrocytic marker.
Methods
Serum from healthy children and adolescents aged 1 to <19 years were obtained from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. Serum NfL (n=300) and GFAP (n=316) were quantified using Simoa technology, and discrete RI (2.5th and 97.5th percentiles) and continuous RI (5th and 95th percentiles) were generated.
Results
While there was no association with sex, there was a statistically significant (p<0.0001) negative association between age and serum NfL (Rho −0.400) and GFAP (Rho −0.749). Two statistically significant age partitions were generated for NfL: age 1 to <10 years (lower, upper limit; 3.13, 20.6 pg/mL) and 10 to <19 years (1.82, 7.44 pg/mL). For GFAP, three statistically significant age partitions were generated: age 1 to <3.5 years (80.4, 601 pg/mL); 3.5 to <11 years (50.7, 224 pg/mL); and 11 to <19 years (26.2, 119 pg/mL).
Conclusions
Taken together with the literature on adults, NfL and GFAP display U-shaped curves with high levels in infants, decreasing levels during childhood, a plateau during adolescence and early adulthood and increasing levels in seniors. These normative data are expected to inform future pediatric studies on the importance of age on neurological blood biomarkers.
Funding source: Canadian Institutes of Health Research
Funding source: Canadian Traumatic Brain Injury Research Consortium
Acknowledgments
We are grateful to all of the CALPER participants and their families and the research and clinical staff that assisted with the study.
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Research ethics: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration and has been approved by the Institutional Review Boards of The Hospital for Sick Children (#1000010867) and Mount Sinai Hospital, Toronto, Canada and The University of British Columbia, Vancouver, Canada (H16-02548).
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Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: The authors report no competing interests.
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Research funding: This study was funded by Canadian Traumatic Brain Injury Research Consortium (CTRC), funded by Brain Canada and the Canadian Institutes of Health Research (to CLW and KA).
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0660).
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